tbuckley/cabot-search huggingface dataset:
An outbreak of cryptosporidiosis associated with drinking water in north-eastern Italy, August 2019: microbiological and environmental investigations
Authors: Armando Franceschelli, Lucia Bonadonna, Simone M Cacciò, Anna Rosa Sannella, Christian Cintori, Raffaele Gargiulo, Anna Maria Coccia, Rosa Paradiso, Marcello Iaconelli, Rossella Briancesco, Alberto Tripodi
Journal: Eurosurveillance (2022)

Cryptosporidium is a leading global cause of waterborne disease, with many reported outbreaks related to main water supplies. In August 2019, an outbreak of cryptosporidiosis involving 80 cases occurred among 114 vacationers in a small municipality located in the Tuscan-Emilian Apennines, north-eastern Italy. After excluding a potential food-borne outbreak, the epidemiological investigation focussed on the hypothesis of a waterborne outbreak. This was confirmed by the finding of Cryptosporidium oocysts in stools of the cases and in water samples from the municipal water network. Molecular characterisation revealed the zoonotic species Cryptosporidium parvum as the causative agent. A single subtype (IIdA25G1) was found among all cases, and in one of two positive water samples. The municipality's water supply used spring water that only received a disinfection treatment insufficient to inactivate the parasite. Possible entry means into the water mains were found through further environmental investigations. As these types of water supplies are particularly vulnerable to various environmental factors, a control system based on the risk assessment of each phase of the water supply chain is required to guarantee water safety. Effective methods for detection of protozoan pathogens, which are generally excluded from routine water supply analysis, should be applied.
The location of the t(4;14) translocation breakpoint within the <i>NSD2</i> gene identifies a subset of patients with high-risk NDMM
Authors: Nicholas Stong, María Ortiz-Estévez, Fadi Towfic, Mehmet Samur, Amit Agarwal, Jill Corre, Erin Flynt, Nikhil Munshi, Hervé Avet-Loiseau, Anjan Thakurta
Journal: Blood (2022)

Although translocation events between chromosome 4 (NSD2 gene) and chromosome 14 (immunoglobulin heavy chain [IgH] locus) (t(4;14)) is considered high risk in newly diagnosed multiple myeloma (NDMM), only ∼30% to 40% of t(4;14) patients are clinically high risk. We generated and compared a large whole genome sequencing (WGS) and transcriptome (RNA sequencing) from 258 t(4;14) (n = 153 discovery, n = 105 replication) and 183 non-t(4;14) NDMM patients with associated clinical data. A landmark survival analysis indicated only ∼25% of t(4;14) patients had an overall survival (OS) <24 months, and a comparative analysis of the patient subgroups identified biomarkers associated with this poor outcome, including translocation breakpoints located in the NSD2 gene and expression of IgH-NSD2 fusion transcripts. Three breakpoints were identified and are designated as: "no-disruption" (upstream of NSD2), "early-disruption" (in the 5' UTR), and "late-disruption" (within the NSD2 gene). Our results show a significant difference in OS based on the location of DNA breakpoints (median OS 28.6 "late-disruption" vs 59.2 "early disruption" vs 75.1 months "no disruption"). These findings have been replicated in an independent replication dataset. Also, univariate and multivariate analysis suggest high-risk markers such as del17p, 1p independently contribute to poor outcome in t(4;14) MM patients.
A method for intelligent allocation of diagnostic testing by leveraging data from commercial wearable devices: a case study on COVID-19
Authors: Md Mobashir Hasan Shandhi, Peter J. Cho, Ali R. Roghanizad, Karnika Singh, Will Wang, Oana M. Enache, Amanda Stern, Rami Sbahi, Bilge Tatar, Sean Fiscus, Qi Xuan Khoo, Yvonne Kuo, Xiao Lu, Joseph Hsieh, Alena Kalodzitsa, Amir Bahmani, Arash Alavi, Utsab Ray, Michael P. Snyder, Geoffrey S. Ginsburg, Dana K. Pasquale, Christopher W. Woods, Ryan J. Shaw, Jessilyn P. Dunn
Journal: npj Digital Medicine (2022)

Mass surveillance testing can help control outbreaks of infectious diseases such as COVID-19. However, diagnostic test shortages are prevalent globally and continue to occur in the US with the onset of new COVID-19 variants and emerging diseases like monkeypox, demonstrating an unprecedented need for improving our current methods for mass surveillance testing. By targeting surveillance testing toward individuals who are most likely to be infected and, thus, increasing the testing positivity rate (i.e., percent positive in the surveillance group), fewer tests are needed to capture the same number of positive cases. Here, we developed an Intelligent Testing Allocation (ITA) method by leveraging data from the CovIdentify study (6765 participants) and the MyPHD study (8580 participants), including smartwatch data from 1265 individuals of whom 126 tested positive for COVID-19. Our rigorous model and parameter search uncovered the optimal time periods and aggregate metrics for monitoring continuous digital biomarkers to increase the positivity rate of COVID-19 diagnostic testing. We found that resting heart rate (RHR) features distinguished between COVID-19-positive and -negative cases earlier in the course of the infection than steps features, as early as 10 and 5 days prior to the diagnostic test, respectively. We also found that including steps features increased the area under the receiver operating characteristic curve (AUC-ROC) by 7-11% when compared with RHR features alone, while including RHR features improved the AUC of the ITA model's precision-recall curve (AUC-PR) by 38-50% when compared with steps features alone. The best AUC-ROC (0.73 ± 0.14 and 0.77 on the cross-validated training set and independent test set, respectively) and AUC-PR (0.55 ± 0.21 and 0.24) were achieved by using data from a single device type (Fitbit) with high-resolution (minute-level) data. Finally, we show that ITA generates up to a 6.5-fold increase in the positivity rate in the cross-validated training set and up to a 4.5-fold increase in the positivity rate in the independent test set, including both symptomatic and asymptomatic (up to 27%) individuals. Our findings suggest that, if deployed on a large scale and without needing self-reported symptoms, the ITA method could improve the allocation of diagnostic testing resources and reduce the burden of test shortages.
Disparities in Vision Health and Eye Care
Authors: Angela R. Elam, Victoria L. Tseng, Tannia M. Rodriguez, Elise V. Mike, Alexis K. Warren, Anne L. Coleman, Ugochi Aguwa, Chrisfouad Alabiad, Cesar Briceno, Hilda Capo, Melissa Contreras, Jane Edmond, Ann-Margret Ervin, Tamara Fountain, David Friedman, James Gao, Lynn Gordon, Joy Harewood, Ken Kitayama, O’Rese Knight, Aaron Lee, Paul Lee, Gary Legault, Kristen Nwanyanwu, Mildred Olivier, Cesar Perez-Gonzalez, Jessica Randolph, Ahmara Ross, Ruth Shoge, Sharon Solomon, Basil Williams, Fasika Woreta, Charles Wright, Nazlee Zebardast
Journal: Ophthalmology (2022)
Extracellular Vesicles in Tissue Engineering: Biology and Engineered Strategy
Authors: Ziyin Pan, Weiyan Sun, Yi Chen, Hai Tang, Weikang Lin, Jiafei Chen, Chang Chen
Journal: Advanced Healthcare Materials (2022)

Extracellular vesicles (EVs), acting as an important ingredient of intercellular communication through paracrine actions, have gained tremendous attention in the field of tissue engineering (TE). Moreover, these nanosized extracellular particles (30-140 nm) can be incorporated into biomaterials according to different principles to facilitate signal delivery in various regenerative processes directly or indirectly. Bioactive biomaterials as the carrier will extend the retention time and realize the controlled release of EVs, which further enhance their therapeutic efficiency in tissue regeneration. Herein, the basic biological characteristics of EVs are first introduced, and then their outstanding performance in exerting direct impacts on target cells in tissue regeneration as well as indirect effects on promoting angiogenesis and regulating the immune environment, due to specific functional components of EVs (nucleic acid, protein, lipid, etc.), is emphasized. Furthermore, different design ideas for suitable EV-loaded biomaterials are also demonstrated. In the end, this review also highlights the engineered strategies, which aim at solving the problems related to natural EVs such as highly heterogeneous functions, inadequate tissue targeting capabilities, insufficient yield and scalability, etc., thus promoting the therapeutic pertinence and clinical potential of EV-based approaches in TE.
Prepregnancy Emergency Department Use and Risks of Severe Maternal and Neonatal Morbidity in Canada
Authors: Catherine E. Varner, Alison L. Park, Joel G. Ray
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Emergency department (ED) use during pregnancy may be associated with worse obstetrical outcomes, possibly because of differences in access to health care. It is not known whether ED use before pregnancy is associated with serious adverse maternal and perinatal outcomes. <h3>Objective</h3> To study the association between prepregnancy ED use and adverse maternal and perinatal outcomes. <h3>Design, Setting, and Participants</h3> This population-based cohort study was conducted in Ontario, Canada, and included all livebirths and stillbirths from April 2003 to January 2020. <h3>Exposures</h3> Main exposure was any ED encounter within 90 days preceding the start of the index pregnancy. <h3>Main Outcomes and Measures</h3> Primary outcome was a composite of severe maternal morbidity (SMM) from 20 weeks' gestation to 42 days' post partum. Secondary outcomes included severe neonatal morbidity (SNM) from 0 to 27 days, neonatal death, and stillbirth. Relative risks (RRs) were adjusted for maternal age, income, and rurality. <h3>Results</h3> Of 2 130 245 births, there were 2 119 335 livebirths (99.5%) and 10 910 stillbirths (0.5%). The mean (SD) maternal age was 29.6 (5.4) years, 212 478 (9.9%) were rural dwelling, and 498 219 (23%) had 3 or more comorbidities. Among all births, 218 011 (9.7%) had a prepregnancy ED visit. The rate of SMM was higher among women with a prepregnancy ED visit than those without (22.3 vs 16.5 per 1000 births), with an RR of 1.34 (95% CI, 1.30-1.38) and an adjusted RR (aRR) of 1.37 (95% CI, 1.33-1.42). Compared with no prepregnancy ED visit, the aRR was higher in those with 1 (1.29; 95% CI, 1.24-1.34), 2 (1.51; 95% CI, 1.42-1.61), and 3 or more (1.74; 95% CI, 1.61-1.90) ED visits. Prepregnancy ED visits for a hematological (aRR, 13.60; 95% CI, 10.48-17.64), endocrine (aRR, 4.96; 95% CI, 3.72-6.62), and circulatory (aRR, 2.27; 95% CI, 1.68-3.07) conditions were associated with the highest aRRs for SMM. The rate of SNM was higher among newborns whose mother visited the ED within 90 days before pregnancy (68.2 vs 55.4 per 1000 births; aRR, 1.24; 95% CI, 1.22-1.26) as was the risk of neonatal death (aRR, 1.26; 95% CI, 1.16-1.37) and stillbirth (aRR, 1.18; 95% CI, 1.11-1.25). <h3>Conclusions and Relevance</h3> In this study, ED use was common before pregnancy. These findings suggest that ED use may not only reflect a woman's access to prepregnancy care but also higher future risk of severe maternal and perinatal morbidity, potentially offering a useful trigger for health system interventions to decrease adverse pregnancy outcomes.
Association of Male Hypogonadism With Risk of Hospitalization for COVID-19
Authors: Sandeep Dhindsa, Cosette Champion, Ekamjit Deol, Matthew Lui, Robert Campbell, Jennifer Newman, Aparna Yeggalam, Srikanth Nadella, Vaishaliben Ahir, Ekta Shrestha, Thomas Kannampallil, Abhinav Diwan
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Male sex is associated with severe COVID-19. It is not known whether the risk of hospitalization differs between men with hypogonadism, men with eugonadism, and those receiving testosterone therapy (TTh). <h3>Objective</h3> To compare COVID-19 hospitalization rates for men with hypogonadism who were not receiving TTh, men with eugonadism, and men receiving TTh. <h3>Design, Setting, and Participants</h3> This cohort study was conducted in 2 large academic health systems in St Louis, Missouri, among 723 men with a history of COVID-19 who had testosterone concentrations measured between January 1, 2017, and December 31, 2021. <h3>Exposures</h3> The primary exposure was gonadal status (hypogonadism, eugonadism, and TTh). Hypogonadism was defined as a total testosterone concentration below the limit of normal provided by the laboratory (which varied from 175 to 300 ng/dL [to convert to nanomoles per liter, multiply by 0.0347]). <h3>Main Outcomes and Measures</h3> The primary outcome was rate of hospitalization for COVID-19. Statistical adjustments were made for group differences in age, body mass index, race and ethnicity, immunosuppression, and comorbid conditions. <h3>Results</h3> Of the 723 study participants (mean [SD] age, 55 [14] years; mean [SD] body mass index, 33.5 [7.3]), 116 men had hypogonadism, 427 had eugonadism, and 180 were receiving TTh. Men with hypogonadism were more likely than men with eugonadism to be hospitalized with COVID-19 (52 of 116 [45%] vs 53 of 427 [12%];<i>P</i> &lt; .001). After multivariable adjustment, men with hypogonadism had higher odds than men with eugonadism of being hospitalized (odds ratio, 2.4; 95% CI, 1.4-4.4;<i>P</i> &lt; .003). Men receiving TTh had a similar risk of hospitalization as men with eugonadism (odds ratio, 1.3; 95% CI, 0.7-2.3;<i>P</i> = .35). Men receiving inadequate TTh (defined as subnormal testosterone concentrations while receiving TTh) had higher odds of hospitalization compared with men who had normal testosterone concentrations while receiving TTh (multivariable adjusted odds ratio, 3.5; 95% CI, 1.5-8.6;<i>P</i> = .003). <h3>Conclusions and Relevance</h3> This study suggests that men with hypogonadism were more likely to be hospitalized after COVID-19 infection compared with those with eugonadism, independent of other known risk factors. This increased risk was not observed among men receiving adequate TTh. Screening and appropriate therapy for hypogonadism need to be evaluated as a strategy to prevent severe COVID-19 outcomes among men.
Megakaryopoiesis impairment through acute innate immune signaling activation by azacitidine
Authors: Ujunwa Cynthia Okoye-Okafor, Komal K. Javarappa, Dimitrios Tsallos, Joseph Saad, Daozheng Yang, Chi Zhang, Lumie Benard, Victor J. Thiruthuvanathan, Sally Cole, Stephen Ruiz, Madhuri Tatiparthy, Gaurav Choudhary, Stefanie DeFronzo, Boris A. Bartholdy, Celine Pallaud, Pedro Marques Ramos, Aditi Shastri, Amit Verma, Caroline A. Heckman, Britta Will
Journal: The Journal of Experimental Medicine (2022)

Thrombocytopenia, prevalent in the majority of patients with myeloid malignancies, such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), is an independent adverse prognostic factor. Azacitidine (AZA), a mainstay therapeutic agent for stem cell transplant–ineligible patients with MDS/AML, often transiently induces or further aggravates disease-associated thrombocytopenia by an unknown mechanism. Here, we uncover the critical role of an acute type-I interferon (IFN-I) signaling activation in suppressing megakaryopoiesis in AZA-mediated thrombocytopenia. We demonstrate that megakaryocytic lineage-primed progenitors present IFN-I receptors and, upon AZA exposure, engage STAT1/SOCS1-dependent downstream signaling prematurely attenuating thrombopoietin receptor (TPO-R) signaling and constraining megakaryocytic progenitor cell growth and differentiation following TPO-R stimulation. Our findings directly implicate RNA demethylation and IFN-I signal activation as a root cause for AZA-mediated thrombocytopenia and suggest mitigation of TPO-R inhibitory innate immune signaling as a suitable therapeutic strategy to support platelet production, particularly during the early phases of AZA therapy.
Progenitor Hierarchy of Chronic Myelomonocytic Leukemia Identifies Inflammatory Monocytic-Biased Trajectory Linked to Worse Outcomes
Authors: Meghan C. Ferrall-Fairbanks, Abhishek Dhawan, Brian Johnson, Hannah Newman, Virginia Volpe, Christopher Letson, Markus Ball, Anthony M. Hunter, Maria E. Balasis, Traci Kruer, Nana Adjoa Ben-Crentsil, Jodi L. Kroeger, Robert Balderas, Rami S. Komrokji, David A. Sallman, Jing Zhang, Rafael Bejar, Philipp M. Altrock, Eric Padron
Journal: Blood Cancer Discovery (2022)

Abstract Myeloblast expansion is a hallmark of disease progression and comprises CD34+ hematopoietic stem and progenitor cells (HSPC). How this compartment evolves during disease progression in chronic myeloid neoplasms is unknown. Using single-cell RNA sequencing and high-parameter flow cytometry, we show that chronic myelomonocytic leukemia (CMML) CD34+ HSPC can be classified into three differentiation trajectories: monocytic, megakaryocyte-erythroid progenitor (MEP), and normal-like. Hallmarks of monocytic-biased trajectory were enrichment of CD120b+ inflammatory granulocyte–macrophage progenitor (GMP)-like cells, activated cytokine receptor signaling, phenotypic hematopoietic stem cell (HSC) depletion, and adverse outcomes. Cytokine receptor diversity was generally an adverse feature and elevated in CD120b+ GMPs. Hypomethylating agents decreased monocytic-biased cells in CMML patients. Given the enrichment of RAS pathway mutations in monocytic-biased cells, NRAS-competitive transplants and LPS-treated xenograft models recapitulated monocytic-biased CMML, suggesting that hematopoietic stress precipitates the monocytic-biased state. Deconvolution of HSPC compartments in other myeloid neoplasms and identifying therapeutic strategies to mitigate the monocytic-biased differentiation trajectory should be explored. Significance: Our findings establish that multiple differentiation states underlie CMML disease progression. These states are negatively augmented by inflammation and positively affected by hypomethylating agents. Furthermore, we identify HSC depletion and expansion of GMP-like cells with increased cytokine receptor diversity as a feature of myeloblast expansion in inflammatory chronic myeloid neoplasms. This article is highlighted in the In This Issue feature, p. 476
Self-reported Alcohol Consumption and Risk of Atrial Fibrillation
Authors: Lars Frost, Renate B. Schnabel
Journal: JAMA Network Open (2022)

Minju Han, MD; So-Ryoung Lee, MD, PhD; Eue-Keun Choi, MD, PhD; JungMin Choi, MD; Jaewook Chung, MD; Sang-Hyeon Park, MD; HuiJin Lee, MD; Hyo-Jeong Ahn, MD; Soonil Kwon, MD; Seung-Woo Lee, BSc; Kyung-Do Han, PhD; Seil Oh, MD, PhD; Gregory Y. H. Lip, MD
Habitual Alcohol Intake and Risk of Atrial Fibrillation in Young Adults in Korea
Authors: Minju Han, So-Ryoung Lee, Eue-Keun Choi, JungMin Choi, Jaewook Chung, Sang-Hyeon Park, HuiJin Lee, Hyo-Jeong Ahn, Soonil Kwon, Seung-Woo Lee, Kyung-Do Han, Seil Oh, Gregory Y. H. Lip
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Guidelines recommend that all risk factors for early-onset atrial fibrillation, including lifestyle factors, be proactively managed, considering the poor prognosis of the disease. Not much is known about the association of cumulative alcohol intake with the risk of atrial fibrillation in young adults aged 20 to 39 years, especially among heavy drinkers. <h3>Objective</h3> To explore the association of alcohol consumption with the risk of incident atrial fibrillation in young adults. <h3>Design, Setting, and Participants</h3> Using the National Health Insurance Service database, a nationwide population-based cohort study of adults aged 20 to 39 years without prior atrial fibrillation who underwent 4 serial annual health examinations between 2009 and 2012 was conducted. The cumulative alcohol consumption burden over 4 years was calculated by assigning 1 point to more than moderate drinking (≥105 g of alcohol per week) each year. Additionally, a semiquantitative cumulative burden was calculated by assigning 0, 1, 2, and 3 points to non, mild (&lt;105 g per week), moderate (105-210 g per week), and heavy (≥210 g per week) drinking, respectively. Data were analyzed from May to June 2021. <h3>Exposure</h3> Amount of alcohol intake in 4 years. <h3>Main Outcomes and Measures</h3> The primary outcome was incident atrial fibrillation during the follow-up period. <h3>Results</h3> A total of 1 537 836 participants (mean [SD] age 29.5 [4.1] years, 1 100 099 [71.5%] male) were included in the final analysis. According to the 4-year cumulative burden of alcohol consumption stratified by moderate to heavy drinking, 889 382 participants (57.8%) were in the burden 0 group, 203 374 participants (13.2%) in the burden 1 group, 148 087 participants (9.6%) in the burden 2 group, 144 023 participants (9.4%) in the burden 3 group, and 152 970 participants (9.9%) in the burden 4 group. During a median (IQR) follow-up of 6.13 (4.59-6.48) years, atrial fibrillation was newly diagnosed in 3066 participants (0.36 per 1000 person-years). Participants with a cumulative burden of 4 points who continued more than moderate drinking for 4 years showed a 25% higher risk of atrial fibrillation compared with 0-point participants who kept non-to-mild drinking over 4 years (adjusted HR, 1.25; 95% CI, 1.12-1.40). In a semiquantitative analysis, participants who sustained heavy drinking for 4 consecutive years were associated with a 47% higher atrial fibrillation risk than those who remained nondrinkers over 4 years (aHR, 1.47, CI 1.18-1.83). <h3>Conclusions and Relevance</h3> Persistent moderate to heavy drinking and higher cumulative alcohol consumption burden might increase the risk of atrial fibrillation even in young adults aged 20 to 39 years.
Error in Byline
Journal: JAMA (2022)

and Development Investment Needed to Bring a New Medicine to Market, 2009Market, -2018," ," published in the March 3, 2020, issue of JAMA, 1 was corrected to update data throughout the article.The data changes originated because of corrections to one of the studies used as a source for clinical trial success rates.In addition to updated data throughout the Original Investigation, accompanying Editorials and Letters necessitated corrections to data. 2-6These articles have been corrected online, and a letter of explanation appears in this issue. 7